ANPEP

Chr 15

alanyl aminopeptidase, membrane

Also known as: AP-M, AP-N, APN, CD13, GP150, LAP1, P150, PEPN

NCBI Gene: 290 ENSG00000166825 UniProt: P15144

Aminopeptidase N is a zinc metalloprotease that cleaves peptides in the intestinal brush border for final protein digestion and processes various peptide hormones and neuropeptides throughout the body. This gene is not well-constrained against loss-of-function variants and currently has no established Mendelian disease associations in pediatric populations. The protein also serves as a receptor for certain coronaviruses and has been implicated in some hematologic malignancies.

ResearchSummary from RefSeq, UniProt

Aminopeptidase N is located in the small-intestinal and renal microvillar membrane, and also in other plasma membranes. In the small intestine aminopeptidase N plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Its function in proximal tubular epithelial cells and other cell types is less clear. The large extracellular carboxyterminal domain contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with known enzymes of this class showed that CD13 and aminopeptidase N are identical. The latter enzyme was thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the CNS. This membrane-bound zinc metalloprotease is known to serve as a receptor for the HCoV-229E alphacoronavirus as well as other non-human coronaviruses. This gene has also been shown to promote angiogenesis, tumor growth, and metastasis and defects in this gene are associated with various types of leukemia and lymphoma. [provided by RefSeq, Apr 2020]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 3.64

OE 0.45 (0.32–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.43Z-score

OE missense 0.83 (0.77–0.90)

492 obs / 589.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.32–0.64)

0≤0.351.4

Missense OE?0.83 (0.77–0.90)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 23 / 51.1Missense obs/exp: 492 / 589.8Syn Z: -1.43

Background carrier burden — how many people carry a rare variant somewhere in ANPEP?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 42

1,266 rare PASS variants

Rare truncating (LoF)

1 in 770

166 rare PASS variants

Rare synonymous (reference)

1 in 58

590 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANPEP. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 58	1 in 740
South Asian	~43k	1 in 45	1 in 2,500
Remaining (unassigned)	~30k	1 in 36	1 in 360
European (Finnish)	~27k	1 in 130	1 in 1,600
Admixed American	~22k	1 in 54	1 in 2,200
African / African American	~21k	1 in 44	1 in 1,100
East Asian	~20k	1 in 45	1 in 720
Ashkenazi Jewish	~13k	1 in 93	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 37	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 20 coding exons well covered in gnomAD exomes and genomes.? see exons ↓